Prefilled container insert for mixing two or more ingredients for use in a pharmaceutical container system

ABSTRACT

The present invention relates to pharmaceutical container systems, and to prefilled container inserts for use therein, for mixing two or more ingredients of a pharmaceutical product. The prefilled container insert of one embodiment comprises a molded container casing having walls, a bottom and an open top for receiving a solid component, a resilient stopper for sealing the open top of the molded container casing, and a bottom disc formed by a weakening rim in the bottom periphery of the molded container casing. The bottom disc is openable to allow mixing of the prefilled solid component with a diluents fluid of the pharmaceutical container system by introducing a spike through the resilient stopper applying a pushing force on the bottom disc, by which force the weakening rim is broken and the container is opened. The prefilled container insert of a further embodiment comprises a molded container casing having walls, a bottom and an open top for receiving an inner open cylinder and a solid component, a resilient stopper for sealing the open top of the molded container casing, and a bottom disc formed by a weakening rim in the bottom periphery of the molded container casing. The bottom disc is openable to allow mixing of the prefilled solid component with a diluents fluid of the pharmaceutical container system by applying a pushing force onto the top of the molded container compressing the casing and forcing the inner cylinder to push on the bottom disc, by which force the weakening rim is broken and the container insert is opened.

TECHNICAL FIELD

The present invention relates to a pharmaceutical multi-chambercontainer system for mixing two or more ingredients of a pharmaceuticalproduct, and more particularly to a pre-filled container insert to beused with such a system.

BACKGROUND OF THE INVENTION

Solid active pharmaceutical ingredients (API) or formulated productsgenerally have better shelf-life, i.e. degrade at a slower rate thansolutions (or dispersions/emulsions) of the same compound. Therefore, itis commonplace to use dry powder, for example to freeze-dry or spray-drypharmaceutical products to extend shelf-life of a pharmaceutical productto practical length, typically at least 18-24 months. At time of use,such a solid product must be dissolved in a suitable solvent before itcan be administered to the patient, usually via is oral or parenteralroutes or by nasal delivery. The dissolution of the solid in a solventis typically made via transfer of the solvent from a vial or bag using asyringe. Although such a process is a standard procedure amongsthospital staff, it does take training and skill to do it in a safe andefficient manner without risk of needle-stick injury or compromisingproduct sterility and thereby patient safety.

Patent abstract of Japan, JP2000037441A relates to an infusion containersystem having a solid drug storing part connected to a liquid solutioncontainer. A fluid communication channel is established between the twocontainers by pressing the solid medicine storing part to the solutioncontainer side and a partitioning member is opened and moved from a sealpart. After making the solid drug storage container and the solutioncontainer open for free passage the solid drug dissolves in the liquidsolution by shaking the whole transfusion container. The solution is nowready to be administered to a patient and a puncture needle isintroduced into an infusion solution take off connection provided in thetop of the solid drug storage container. A drawback with this device isthat it requires a complicated construction of the solid drug storingpart comprising several parts and which will involve a number ofproduction steps. A further drawback is that two steps need to becarried out before the solution can be administered to a patient, namelyfirst allow for mixing of the two ingredients and then introducing aneedle to connect for example an infusion set.

THE OBJECT OF THE INVENTION

It is an object of the present invention, in preferred embodiments atleast, to provide a container system in which mixing of two or moreingredients of a pharmaceutical product, e.g. a solid and solvent or twodifferent liquids, is made using a simple, effective and intuitiveprocedure with minimum risks for hospital staff and patients.

It is a further object of the present invention, in preferredembodiments at least, to provide a robust concept to be used inconnection with blow-fill-seal (BFS) equipment having a constructioninvolving few parts as well as few production steps.

SUMMARY OF THE INVENTION

In accordance with the present invention, from a first broad aspect atleast, there is provided a pre-filled container insert for use in apharmaceutical container system for mixing two or more ingredients of apharmaceutical product. The pre-filled container insert comprises;

a moulded container casing having walls, bottom and an open top forreceiving a solid component,

a resilient stopper for sealing the open top of the moulded containercasing,

a bottom disc formed by a weakening rim in the bottom periphery of themoulded container casing, wherein the bottom disc is openable to allowmixing of the pre-filled solid component with a diluents fluid of thepharmaceutical container system by introducing a spike through theresilient stopper applying a pushing force on the bottom disc, by whichforce the weakening rim is broken and the container insert is opened.

In accordance with the present invention, from a further broad aspect atleast, there is provided a pre-filled container insert for use in apharmaceutical container system for mixing two or more ingredients of apharmaceutical product. The pre-filled container insert comprises;

a moulded container casing having walls, bottom and an open top forreceiving an inner open cylinder and a solid component,

a resilient stopper for sealing the open top of the moulded containercasing,

a bottom disc formed by a weakening rim in the bottom periphery of themoulded container casing, wherein the bottom disc is openable to allowmixing of the pre-filled solid component with a diluents fluid of thepharmaceutical container system by applying a pushing force onto the topof the moulded container, thereby compressing the casing and forcing theinner cylinder towards the bottom disc, by which force the weakening rimis broken and the container insert is opened.

An advantage of preferred embodiments of the present invention is thatthere is provided a pre-filled container insert that is constructed froma minimum of parts and at the same time has efficient and robustconstruction. A further advantage of preferred embodiments of thepresent invention is that there is provided a pre-filled containerinsert that easily can be opened to provide mixing of contents in theinsert and the liquids container. A still further advantage is that thepre-filled container insert is manufactured as a separate device and canbe incorporated into different types of blow-fill-seal containersforming a pharmaceutical multi-chamber container system. Yet anotheradvantage is that the separate device can be aseptically filled, sealedand processed (e.g. terminally sterilised) under controlled conditionsbefore the next unit operation of actually mounting the device into thediluents container.

According to preferred embodiments of the invention, the weakening rimin the bottom disc is arranged around the periphery of the bottom of thecontainer casing forming a hinged disc such that the bottom disc remainsconnected to the container casing when the weakening rim is broken andthe container is opened.

In this way the bottom disc is prevented from falling out into thediluents container after opening of the pre-filled container insert.

According to preferred embodiments of the invention, the resilientstopper is secured in place by a clamp ring to hermetically seal the topopening.

The clamp ring locks and fixes the resilient stopper in the open top ofthe container casing and the moulded casing is hermetically sealed.

According to preferred embodiments of the invention, the bottom disc iscovered by a moisture barrier foil.

According to preferred embodiments of the invention, the resilientstopper is covered by a moisture barrier foil.

By covering the container insert with a moisture barrier foil, both onthe bottom side or on the resilient top side, the pre-filled content hasa maximum of protection from the outside environment, i.e. light,moisture and/or oxygen.

According to preferred embodiments of the invention, the pre-filledcontainer insert is aseptically mounted into the top of a BFS-containerforming a multi-chamber pharmaceutical container system.

According to preferred embodiments of the invention, the mouldedcontainer casing has pleated sidewalls forming a bellows containerinsert.

By forming the container casing as a bellows container an easilydeformable casing is formed in one single piece.

According to preferred embodiments of the invention, the pre-filledcontainer insert is capable of use with one or more delivery systems,such as a nasal delivery system. Preferably the pre-filled containerinsert is connectable to or within, or otherwise can be incorporatedwith, for example, a standard nasal delivery mechanism such as a nasalspray.

According to preferred embodiments of the invention, there is provided apharmaceutical container system for mixing two or more ingredients of apharmaceutical product, comprising

a first container comprising a diluents liquid,

a second container insert aseptically mounted into the top of the firstcontainer, the second container comprising

a moulded container casing for receiving a solid component,

a resilient stopper for sealing the open top of the moulded containercasing,

a bottom disc formed by a weakening rim in the bottom periphery of themoulded container casing, wherein the bottom disc is openable to allowmixing of the pre-filled solid component with a diluents fluid of thepharmaceutical container system by introducing a spike through theresilient stopper applying a pushing force on the bottom disc, by whichforce the weakening rim is broken and the container insert is opened.

According to preferred embodiments of the invention, there is provided apharmaceutical container system for mixing two or more ingredients of apharmaceutical product comprising

a first container comprising a diluents liquid,

a second container insert aseptically mounted into the top of the firstcontainer, the second container comprising

a moulded container casing having walls, bottom and an open top forreceiving an inner open cylinder and a solid component,

a resilient stopper for sealing the open top of the moulded containercasing,

a bottom disc formed by a weakening rim in the bottom periphery of themoulded container casing, wherein the bottom disc is openable to allowmixing of the pre-filled solid component with a diluents fluid of thepharmaceutical container system by applying a pushing force onto the topof the moulded container, thereby compressing the casing and forcing theinner cylinder towards the bottom disc, by which force the weakening rimis broken and the container insert is opened.

A standard procedure for a nurse preparing an intra-venous(IV)-container is to visually inspect, and in some procedures to spike,the IV-container before starting infusion. Therefore, using apharmaceutical container system according to embodiments of the presentinvention, the standard working procedure is not changed. In preferredembodiments, by simply pushing the container top to allow mixing andthen ensure the complete mixing operation by visual inspection, a simplean intuitive procedure is obtained. In addition, no separate mixing stepusing hypodermic needles are necessary, eliminating the risk ofneedle-stick injuries. Mixing is made without risk of microbialcontamination since the solid and liquid chambers are both parts of thesame hermetically sealed container. In other embodiments, similar stepsare carried out but for preparing a nasal delivery device such as anasal spray, which typically comprises a container, and a spray or othernasal delivery mechanism attached thereto.

Medicaments suitable for administration via a pharmaceuticalmulti-chamber container system for mixing two or more ingredients of apharmaceutical product, and more particularly to be pre-filled with thecontainer insert of the present invention include for example protonpump inhibitors, for example omeprazol, anticancer medicaments,antibiotics, immunotherapies, vaccines, antiviral medicaments,polypeptides and peptides, for example, peptide hormones and growthfactors, polypeptide vaccines, enzymes endorphines, lipoproteins andpolypeptides involved in the blood coagulation cascade.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will now be described, for exemplary purposes, inmore detail by way of embodiments and with reference to the encloseddrawings, in which: FIGS. 1 a-1 g illustrate schematically themanufacturing steps of a pre-filled container insert in accordance witha preferred embodiment of the present invention, and,

FIGS. 2 a and 2 b schematically illustrate the opening procedure of thepre-filled container insert, and,

FIGS. 3 a-3 d show a pharmaceutical container system for mixing two ormore ingredients s of a pharmaceutical product, which system consists ofa BFS-container filled with a diluents liquid and a pre-filled insertsealed to the container, and,

FIGS. 4 a-4 h illustrate schematically the manufacturing steps of afurther pre-filled container insert in accordance with a preferredembodiment of the present invention, and,

FIGS. 5 a-5 c schematically illustrate the opening procedure of thepre-filled container insert of FIGS. 4 a-4 h, and;

FIGS. 6 a-6 d show a pharmaceutical container system for mixing two ormore ingredients of a pharmaceutical product, which system consists of aBFS-container filled with a diluents liquid and a pre-filled insertsealed to the container.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

FIGS. 1 a to 1 g and 4 a to 4 h schematically illustrate how pre-filledcontainer inserts can be manufactured. The container inserts, beingmanufactured separately e.g. by injection moulding can use any typethermoplastic material, e.g. high-barrier engineering plastics ifnecessary to impart high-barrier properties, e.g. with light, moistureor oxygen sensitive compounds.

FIG. 1 a shows the moulded container casing 1 having walls 2, bottom 3and an open top 4 for receiving a medicament component. The containercasing 1 which is made using e.g. injection moulding preferably has acylindrical geometry and the bottom 3 has a suitable weakening rim 5 inthe bottom periphery. The weakening rim 5 will make it possible to pushopen the bottom disc 3 to allow material transfer between the pre-filledinsert and a liquid container. Preferably, a small portion of theweakening rim is kept thicker, functioning as a hinge 6 so as to preventthe bottom disc 3 to completely disengage from the solids container onopening.

To further augment the moisture or gas barrier of the container insertand thus to protect the content, a barrier foil 7, e.g. an aluminiumfoil can be used to cover the bottom disc 3, which can be seen in FIG. 1b.

In FIG. 1 c the moulded container casing is pre-filled with a content 8,a powder or other suitable solid (or semi-solid) in a well-defined,clean environment (e.g. aseptic filling in isolator or other suitableuni directional air flow hood (UDF)). According to another aspect ofthis invention not shown in the drawings, the moulded container casingis pre-filled with a semi-solid content or a liquid, which is to bemixed with the diluents prior to infusion.

FIGS. 1 d, 1 e and 1 f show how the container insert is hermeticallyclosed using a resilient stopper 9, e.g. a standard rubber stopper orthermoplastic elastomer (TPE) part, which is mounted through the opentop and secured by a clamp ring 10 to ensure a safe and tight fasteningof the stopper 9. As shown in FIG. 1 g, a barrier foil 15, i.e. analuminium foil, can be used to cover the resilient stopper 9 and clampring 10 to further augment the moisture or gas barrier of the pre-filledcontainer insert 17. The open centre of the clamp ring 10 reveals acircular area of the resilient stopper where the spike (or a punctureneedle) can be entered through the stopper. The pre-filled containerinsert 17 can be sterilised either in-line or in a separate step afterfilling/closing using standard methods such as e-beam or gammairradiation. Such a sterile pre-filled container insert can then betransported to a suitable standard filling line for liquids to bemounted to a blow-fill-seal container or other suitable liquids plasticcontainer. The container may comprise a component of a nasal deliverydevice, which preferably contains the appropriate liquid.

FIG. 2 a schematically illustrate how a spike 20 is pushed through theresilient stopper 9 of the pre-filled container insert and in 2 b howthe pushing force from the spike 20 breaks the weakened rim 5 in bottomperiphery (as well as the barrier foil 7) and the content 8 of thepre-filled container insert is free to leave the container.

FIG. 3 a illustrates an embodiment of a pharmaceutical container system21 wherein a pre-filled container insert 17 according to the presentinvention is mounted into the top of a blow-fill-seal container 22. Inthe embodiment of FIGS. 3 a to 3 d, the system 21 comprises meanssuitable for intravenous delivery of a medicament, but the system maycomprise any other, suitable pharmaceutical system, such as a container(e.g. a bottle, vial or tube) for use with a nasal delivery mechanism,e.g. a spray or dropper that connects to the container. The pre-filledcontainer insert 17 of the FIG. 3 a embodiment filled with a content 8will be enclosed into the liquid blow-fill-seal container and the topportion of the pre-filled container is revealed to the user by opening atwist-off top 23 of the blow-fill-seal container 22, which is shown inFIG. 3 b. In a preferred embodiment, also shown in FIG. 3 b, a moisturebarrier seal 15 covers the top, i.e. a resilient stopper 9 of thepre-filled container under the twist-off top 23. After the moisturebarrier seal 15 has been removed the content 8 of the pre-filledcontainer insert 17 is ready to be mixed with the diluents fluid in theblow-fill-seal container 22. FIG. 3 c shows how a spike 20 punctures theresilient stopper 9 and enters into the pre-filled container 17. Thepushing force from the spike 20 acts on the bottom disc 3 and theweakened rim 5 in the periphery of the disc breaks up. The disc 3 isprevented from falling out into the blow-fill-seal container 22 by ahinge 6 connecting the bottom disc to the wall 2 of the containerinsert. The content of the pre-filled container can now be mixed withthe diluents fluid of the blow-fill-seal container by gentle shaking thecontainer. In FIG. 3 d a bottom flap 25 is pulled up to allow hanging ofthe container system near a patient while administering the substance tothe patient. According to another aspect of the present invention notshown in the drawings, the pre-filled container insert is welded into aflexible bag wall being filled with the diluents liquid.

FIG. 4 a shows another embodiment of the present invention. Likereference numerals are used to indicate components similar to those ofthe embodiment of FIGS. 1 to 3. The moulded container casing 1 has walls2, bottom 3 and an open top 4 for receiving a medicament component. Thecontainer casing 1 which is made using e.g. injection mouldingpreferably has a cylindrical geometry and differs from the previousembodiment in that the walls 2 are pleated such that the containercasing has the form of a bellows. The bottom 3 has a suitable weakeningrim 5 in the bottom periphery. Preferably, a small portion of theweakening rim is kept thicker, functioning as a hinge 6 so as to preventthe bottom disc 3 to completely disengage from the solids container onopening. To further augment the moisture or gas barrier of the containerinsert and thus to protect the content, a barrier foil 7, e.g. analuminium foil can be used to cover the bottom disc 3, which can be seenin FIG. 4 b.

In FIG. 4 c an inner cylinder 30 is placed inside the moulded containercasing and, as shown in FIG. 4 d, the inner cylinder placed within thecontainer walls is then pre-filled with a content 8, a powder or othersuitable solid (or semi-solid) in a well-defined, clean environment(e.g. aseptic filling in isolator or other suitable uni directional airflow hood (UDF)). According to another aspect of this invention notshown in the drawings, the inner cylinder with container is pre-filledwith a semi-solid content or a liquid which is to is be mixed with thediluents prior to infusion. The weakening rim 5 will make it possible topush open the bottom disc 3 using the inner cylinder 30 to allowmaterial transfer between the pre-filled insert and a liquid container.The inner cylinder 30 is tapered and oriented in relation to theweakening rim so that the tapered end push first at the positiondirectly opposite the hinge part of the weakening rim along theperiphery.

FIGS. 4 e and 4 f show how the container insert is hermetically closedusing a resilient stopper 9, e.g. a standard rubber stopper orthermoplastic elastomer (TPE) part, which is mounted through the opentop and secured by a clamp ring 10 to ensure a safe and tight fasteningof the stopper 9. As shown in FIG. 4 h, a barrier foil 15, i.e. analuminium foil, can be used to cover the resilient stopper 9 and clampring 10 to further augment the moisture or gas barrier of the pre-filledcontainer insert 17. Alternatively, the aluminium foil is replaced witha standard tamper-evident protective seal. The open centre of the clampring 10 reveals a circular area of the resilient stopper where the spike(or a puncture needle) can be entered through the stopper. Thepre-filled container insert 17 can be sterilised either in-line (atfilling) or in a separate step after filling/closing using standardmethods such as e-beam or gamma irradiation. Such a sterile pre-filledcontainer insert can then be transported to a suitable standard fillingline for liquids to be mounted to a blow-fill-seal container or othersuitable liquids plastic container.

FIG. 5 a schematically illustrates how a pressing force is applied tothe top of the bellows container insert 17 and how the pushing forcecompresses the walls 2 of the container insert. In FIG. 5 b the innercylinder 30 presses on the bottom 3 and breaks the weakened rim 5 inbottom periphery (as well as the barrier foil 7) and the content 8 ofthe pre-filled container insert is free to leave the container and bemixed with a diluent fluid (not shown). In FIG. 5 c a spike 20 isintroduced through the rubber stopper 9 to make the container ready foradministration to a patient.

FIG. 6 a illustrates an embodiment of a pharmaceutical container system21 wherein a pre-filled container insert 17 according to the presentinvention is mounted into the top of a is blow-fill-seal container 22.As discussed above, the system may comprise any other, suitablepharmaceutical system, such as a container for use with a nasal deliverymechanism. The pre-filled container insert 17 filled with a content 8will be enclosed into the liquid blow-fill-seal container and the topportion of the pre-filled container is revealed to the user by opening atwist-off top 23 of the blow-fill-seal container 22, which is shown inFIG. 6 b. In a preferred embodiment, also shown in FIG. 6 b, a moisturebarrier seal 15 covers the top, i.e. a resilient stopper 9 of thepre-filled container under the twist-off top 23. After removal of thetwist-off top the content 8 of the pre-filled container insert 17 isready to be mixed with the diluents fluid in the blow-fill-sealcontainer 22. FIG. 6 c shows how the walls 2 of the bellows insert arecompressed. The pushing force makes the inner cylinder 30 to break theweakened rim 5 in the periphery of the bottom disc 3 and the rim breaksup. The disc 3 is prevented from falling out into the blow-fill-sealcontainer 22 by a hinge 6 connecting the bottom disc to the wall 2 ofthe container insert. The content of the pre-filled container can now bemixed with the diluents fluid of the blow-fill-seal container by gentleshaking of the container. After visual inspection to ensure completemixing of the contents and confirmation of the absence of particulates,the moisture barrier seal (or tamper-evident seal) can be removed. Aspike 20 (or puncture needle) may be introduced through the stopper 9 tomake the container ready to be administered to a patient. According toanother aspect of the present invention not shown in the drawings, thepre-filled container insert is welded into a flexible bag wall beingfilled with the diluents liquid.

To mix the content of the solid and liquid containers in the aboveintravenous examples, the user (typically a nurse) adopts a normalworking procedure with intravenous, i.e. IV-infusions. A preferred useof a system in accordance with an embodiment of the present invention asillustrated in FIGS. 1 to 3 is described below in chronological order.

1) The nurse twists off the blow-fill seal container top and peels offthe moisture barrier seal if there is one (and disinfects the rubberstopper top if that is standard procedure).

2) A sterile IV-administration set bag is opened.

3) The IV-spike of the administration set is inserted into the rubberstopper top, thereby piercing the rubber stopper. As the spike is fullyinserted, the bottom disc of the solids chamber is pushed open by thespike, and the solids and liquids chambers are now communicating toenable mixing.

4) The contents of the solids and liquids chambers are mixed by gentlyrocking the container.

5) The nurse visually inspects the contents of the container to ensurefull dissolution and absence of particulate matter.

6) The needle is attached to the patient after purging, and IV-infusionis ready to start.

A preferred use of a system in accordance with another embodiment of thepresent invention as illustrated in FIGS. 4 to 6 is described below inchronological order.

1) The nurse twists off the blow-fill seal container top.

2) The nurse compresses the bellows insert to make the pre-filledcontent fall into the diluents container and the solids and liquidschambers are now communicating to enable mixing.

3) The contents of the solids and liquids chambers are mixed by gentlyrocking the container.

4) The nurse peels off the moisture barrier (or protective) seal anddisinfects the rubber stopper top if that is standard procedure

4) A sterile IV-administration set bag is opened. The IV-spike of theadministration set is inserted into the rubber stopper top, therebypiercing the rubber stopper.

5) The nurse visually inspects the contents of the container to ensurefull dissolution and absence of particulate matter.

6) The needle is attached to the patient after purging, and IV-infusionis ready to start.

In other embodiments, for example where the pre-filled insert is for usewith, e.g., a nasal is delivery device, some of the above steps may becarried out, but with the insert contained within, or otherwiseassociated with, a suitable container such as a nasal spray bottle orthe like.

Further, it will be understood that the present invention is not limitedto the described embodiments but can be modified in many different wayswithout departing from the scope of the appended claims.

1. A prefilled container insert for use in a pharmaceutical containersystem for mixing two or more ingredients of a pharmaceutical product,the pre-filled container insert comprising: a molded container casinghaving walls, a bottom and an open top for receiving a solid component;a resilient stopper for sealing the open top of the molded containercasing; and a bottom disc formed by a weakening rim in the bottomperiphery of the molded container casing, wherein the bottom disc isopenable to allow mixing of the pre-filled solid component with adiluents fluid of the pharmaceutical container system by introducing aspike through the resilient stopper applying a pushing force on thebottom disc, by which force the weakening rim is broken and thecontainer insert is opened.
 2. A prefilled container insert for use in apharmaceutical container system for mixing two or more ingredients of apharmaceutical product, the pre-filled container insert comprising: amolded container casing having walls, a bottom and an open top forreceiving an inner open cylinder and a solid component; a resilientstopper for sealing the open top of the molded container casing; and abottom disc formed by a weakening rim in the bottom periphery of themolded container casing, wherein the bottom disc is openable to allowmixing of the pre-filled solid component with a diluents fluid of thepharmaceutical container system by applying a pushing force onto the topof the molded container, thereby compressing the casing and forcing theinner cylinder towards the bottom disc, by which force the weakening rimis broken and the container insert is opened.
 3. A prefilled containerinsert according to claim 2, wherein the molded container casing haspleated sidewalls forming a bellows container insert.
 4. A prefilledcontainer insert according to claim 1, wherein the weakening rim in thebottom disc is arranged around the periphery of the bottom of thecontainer casing forming a hinged disc such that the bottom disc remainsconnected to the container casing when the weakening rim is broken andthe container is opened.
 5. A prefilled container insert according toclaim 1, wherein the resilient stopper is secured in place by a clampring to hermetically seal the top opening.
 6. A pre-filled prefilledcontainer insert according to claim 1, wherein the bottom disc iscovered by a moisture barrier foil.
 7. A prefilled container insertaccording to claim 1, wherein the resilient stopper is covered by amoisture barrier foil.
 8. A prefilled container insert according toclaim 1, wherein the prefilled container insert is aseptically mountedinto the top of a Blow-Fill-Seal (BFS) container forming a multi-chamberpharmaceutical container system.
 9. A prefilled container insertaccording to claim 1, wherein the prefilled container insert isaseptically mounted into a container, the container having a deliverymechanism capable of attachment thereto, such that there is provided amulti-chamber pharmaceutical delivery system.
 10. A prefilled containerinsert according to claim 9, wherein the delivery mechanism comprises anasal delivery component, preferably a spray, dropper or the like.
 11. Apharmaceutical container system for mixing two or more ingredients of apharmaceutical product, comprising: a first container comprising adiluents liquid; and a second container insert aseptically mounted intothe top of the first container, the second container including: a moldedcontainer casing for receiving a solid component; a resilient stopperfor sealing the open top of the molded container casing; and a bottomdisc formed by a weakening rim in the bottom periphery of the moldedcontainer casing, wherein the bottom disc is openable to allow mixing ofthe prefilled solid component with a diluents fluid of thepharmaceutical container system by introducing a spike through theresilient stopper applying a pushing force on the bottom disc, by whichforce the weakening rim is broken and the container is opened.
 12. Apharmaceutical container system for mixing two or more ingredients of apharmaceutical product, comprising: a first container comprising adiluents liquid; and a second container insert aseptically mounted intothe top of the first container, the second container including: a moldedcontainer casing having walls, a bottom and an open top for receiving aninner open cylinder and a solid component; a resilient stopper forsealing the open top of the molded container casing; and a bottom discformed by a weakening rim in the bottom periphery of the moldedcontainer casing, wherein the bottom disc is openable to allow mixing ofthe prefilled solid component with a diluents fluid of thepharmaceutical container system by applying a pushing force onto the topof the molded container, thereby compressing the casing and forcing theinner cylinder towards the bottom disc, by which force the weakening rimis broken and the container insert is opened.